Zhou Tian-Biao, Zeng Zhi-Yu, Qin Yuan-Han, Zhao Yan-Jun
Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Department of Cardiology/Geriatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Int J Mol Sci. 2012;13(8):9808-9825. doi: 10.3390/ijms13089808. Epub 2012 Aug 6.
Prohibitin (PHB) and paired box 2 (PAX2) are associated with the development of renal interstitial fibrosis (RIF). This study was performed to investigate whether or not the PHB could regulate the PAX2 gene expression in unilateral ureteral obstruction (UUO) in rats. Eighty Wistar male rats were randomly divided into two groups: sham operation group (SHO) and model group subjected to unilateral ureteral obstruction (GU), n = 40, respectively. The model was established by left ureteral ligation. Renal tissues were collected at 14-day and 28-day after surgery. RIF index, protein expression of PHB, PAX2, transforming growth factor-βl (TGF-β1), α-smooth muscle actin (α-SMA), collagen-IV (Col-IV), fibronectin (FN) or cleaved Caspase-3, and cell apoptosis index in renal interstitium, and mRNA expressions of PHB, PAX2 and TGF-β1 in renal tissue were detected. When compared with those in SHO group, expression of PHB (mRNA and protein) was significantly reduced, and expressions of PAX2 and TGF-β1 (protein and mRNA) were markedly increased in the GU group (each p < 0.01). Protein expressions of α-SMA, Col-IV, FN and cleaved Caspase-3, and RIF index or cell apoptosis index in the GU group were markedly increased when compared with those in the SHO group (each p < 0.01). The protein expression of PHB was negatively correlated with protein expression of PAX2, TGF-β1, α-SMA, Col-IV, FN or cleaved Caspase-3, and RIF index or cell apoptosis index (all p < 0.01). In conclusion, less expression of PHB is associated with increased PAX2 gene expression and RIF index in UUO rats, suggesting that increasing the PHB expression is a potential therapeutic target for prevention of RIF.
抗增殖蛋白（PHB）和配对盒基因2（PAX2）与肾间质纤维化（RIF）的发生发展有关。本研究旨在探讨PHB是否能调节大鼠单侧输尿管梗阻（UUO）模型中PAX2基因的表达。80只雄性Wistar大鼠随机分为两组：假手术组（SHO）和单侧输尿管梗阻模型组（GU），每组n = 40只。通过左侧输尿管结扎建立模型。术后14天和28天收集肾组织。检测RIF指数、肾间质中PHB、PAX2、转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）、IV型胶原（Col-IV）、纤连蛋白（FN）或裂解的半胱天冬酶-3的蛋白表达以及细胞凋亡指数，以及肾组织中PHB、PAX2和TGF-β1的mRNA表达。与SHO组相比，GU组中PHB（mRNA和蛋白）表达显著降低，PAX2和TGF-β1（蛋白和mRNA）表达显著升高（各p < 0.01）。与SHO组相比，GU组中α-SMA、Col-IV、FN和裂解的半胱天冬酶-3的蛋白表达以及RIF指数或细胞凋亡指数显著升高（各p < 0.01）。PHB蛋白表达与PAX2、TGF-β1、α-SMA、Col-IV、FN或裂解的半胱天冬酶-3的蛋白表达以及RIF指数或细胞凋亡指数呈负相关（均p < 0.01）。总之，UUO大鼠中PHB表达降低与PAX2基因表达增加及RIF指数升高有关，提示增加PHB表达可能是预防RIF的潜在治疗靶点。
